3-12807306-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001162499.2(CAND2):​c.213C>T​(p.Cys71Cys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000542 in 1,551,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

CAND2
NM_001162499.2 splice_region, synonymous

Scores

2
Splicing: ADA: 0.4512
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01
Variant links:
Genes affected
CAND2 (HGNC:30689): (cullin associated and neddylation dissociated 2 (putative)) Predicted to enable TBP-class protein binding activity. Predicted to be involved in SCF complex assembly; positive regulation of transcription, DNA-templated; and protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 3-12807306-C-T is Benign according to our data. Variant chr3-12807306-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3263106.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.01 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAND2NM_001162499.2 linkc.213C>T p.Cys71Cys splice_region_variant, synonymous_variant Exon 3 of 15 ENST00000456430.6 NP_001155971.1 O75155-1
CAND2XM_011533504.3 linkc.141C>T p.Cys47Cys splice_region_variant, synonymous_variant Exon 3 of 15 XP_011531806.1
CAND2XM_011533503.3 linkc.213C>T p.Cys71Cys splice_region_variant, synonymous_variant Exon 3 of 14 XP_011531805.1
CAND2NM_012298.3 linkc.213-2753C>T intron_variant Intron 2 of 12 NP_036430.1 O75155-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAND2ENST00000456430.6 linkc.213C>T p.Cys71Cys splice_region_variant, synonymous_variant Exon 3 of 15 1 NM_001162499.2 ENSP00000387641.2 O75155-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152146
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000128
AC:
20
AN:
155690
Hom.:
0
AF XY:
0.000133
AC XY:
11
AN XY:
82474
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000407
Gnomad ASJ exome
AF:
0.000237
Gnomad EAS exome
AF:
0.00138
Gnomad SAS exome
AF:
0.0000440
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000167
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000565
AC:
79
AN:
1398922
Hom.:
0
Cov.:
29
AF XY:
0.0000507
AC XY:
35
AN XY:
689940
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.0000796
Gnomad4 EAS exome
AF:
0.000812
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000464
Gnomad4 OTH exome
AF:
0.000724
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152146
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000174
Hom.:
0
Bravo
AF:
0.0000945
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 06, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
17
DANN
Benign
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.45
dbscSNV1_RF
Benign
0.51
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1054069122; hg19: chr3-12848805; API